Exercise to Improve Neurovascular Function in Breast Cancer Survivors

Study Rationale: Breast cancer survivors are more likely to develop cardiovascular disease (CVD) or neurocognitive disease than age-matched counterparts without a history of cancer diagnosis. Some anti-cancer treatments cause damage to the cells of heart and the walls of blood vessels, which may exacerbate neurovascular dysfunction and cancer-related cognitive impairment (symptoms such as 'chemo-brain'), as well as accelerating the onset of neurocognitive disease. Therefore, effective policies and therapeutic strategies are needed to minimize neurovascular dysfunction and neurocognitive disease in at-risk populations like breast cancer survivors. Regular exercise training is effective in slowing or preventing the development of CVD. Furthermore, higher fitness levels are associated with lower dementia risk in older adults, which may be due to better neurovascular function. However, whether exercise training incorporated into a Cardio-Oncology Rehabilitation and Exercise (CORE) programme can improve neurovascular function in breast cancer survivors is currently unknown. Therefore, the primary aim of this study will be to determine the effect of a CORE programme on neurovascular function in long-term breast cancer survivors. Study Description: This study will be a randomised controlled trial to investigate the effect of a CORE programme on neurovascular function in long-term breast cancer survivors. Participants will complete a series of baseline assessments, including lifestyle questionnaires, a cognitive function assessment, dual-energy x-ray absorptiometry (DXA), a cardiopulmonary exercise test (CPET), ultrasound assessments of arterial stiffness and vascular function, and brain magnetic resonance imaging (MRI). Furthermore, participants will wear a blood pressure monitor at home for 24 hours, and a physical activity monitor for seven days. Following completion of baseline assessments, participants will be randomised to either the CORE program or a 'usual care' group. The CORE program will include a 6-month exercise training program supervised by an Exercise Physiologist at the Baker Heart and Diabetes Institute. The usual care group will carry on with healthcare from their usual healthcare provider(s) for 6 months. Participants will then complete two follow-up study visits following completion of the 6-month intervention period, with identical procedures to the baseline study visits. Study Duration: This study involves two baseline study visits in month 1, followed by two study visits in month 7. Participants randomised to the CORE program will be asked to attend the Baker Heart and Diabetes Institute on a weekly basis for supervised exercise training sessions. However, the supervised exercise training sessions will be provided by a mix of in-person, video-conferencing and tele-health modes depending on each participants availability and needs.

Sex

Female

Minimum age

45 Years

Maximum age

75 Years

Inclusion Criteria:

* Female
* Aged 45 - 75 years old at study enrolment
* Diagnosed with stage 1 - 3 breast cancer 5 - 10 years prior to study enrolment
* Have received potentially toxic chemotherapy, including:

  * Anthracycline (any dose)
  * Trastuzumab (Herceptin) in breast-cancer with the HER2 mutation OR
  * Tyrosine kinase inhibitors (e.g. sunitinib) OR
  * Left chest radiotherapy
* ≥ 1 'traditional' CVD risk factor (I.e., Hypertension, dyslipidaemia, diabetes, obesity, smoking or family history of CVD) (Mehta et al., 2023)
* 'Physically inactive', not meeting Australian physical activity guidelines for adults or regularly participating in structured exercise training (Care, 2024).
* Eligible for Medicare
* Willing to provide written informed consent to participate in the study

Exclusion Criteria:

* Diagnosed CVD or stage B heart failure
* Diagnosed neurocognitive or cerebrovascular disease
* Diagnosed atrial fibrillation or cardiac arrythmia
* BMI ≤ 18.4 kg∙m2
* Any other contraindications to exercise testing and training that make participation in this study unsafe, determined through medical screening
* Unable to speak and understand the English language
* Contraindication to brain MRI
* Participating in another clinical research trial where randomized treatment would be unacceptable
* Oncologic (or other) life expectancy ≤ 12 months or any other medical condition (including pregnancy) that results in the belief (deemed by the Principal Investigator) that it is not appropriate for the patient to participate in this trial.